Multiple interactive factors in hepatocarcinogenesis

Cancer Letters

Volumn 346, Issue 1, 2014, Pages 17-23

  Ding, Jin ^a,b   Wang, Hongyang ^a,b  

^a SECOND MILITARY MEDICAL UNIVERSITY   (China)

^b National Scientific Centre for Liver Cancer   (China)

Author keywords

Hepatitis virus; Hepatocarcinogenesis; Inflammation; Liver tumor initiating cell

Indexed keywords

AXIN; BETA CATENIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; K RAS PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P53; RETINOBLASTOMA BINDING PROTEIN 1; SOMATOMEDIN B RECEPTOR;

ALCOHOL LIVER DISEASE; CHINA; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENOMIC INSTABILITY; HEPATITIS B; HEPATITIS C; HEPATITIS VIRUS; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; NONALCOHOLIC FATTY LIVER; PRIORITY JOURNAL; RISK FACTOR; SHORT SURVEY; TUMOR MICROENVIRONMENT;

HEPATITIS B VIRUS; HEPATITIS C VIRUS;

HEPATITIS VIRUS; HEPATOCARCINOGENESIS; INFLAMMATION; LIVER TUMOR INITIATING CELL;

CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; LIVER NEOPLASMS;

EID: 84896706849     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2013.12.024     Document Type: Review

References (106)

1. Hashem B. Current Concepts Hepatocellular Carcinoma. N. Engl. J. Med. 2011, 365:1118-1127.
2. Tornesello M.L., Buonaguro L., Tatangelo F., Botti G., Izzo F., Buonaguro F.M. Mutations in TP53, CTNNB1 and PIK3CA genes in hepatocellular carcinoma associated with hepatitis B and hepatitis C virus infections. Genomics 2013, 102:74-83.
3. Hussain S.P., Schwank J., Staib F., Wang X.W., Harris C.C. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 2007, 26:2166-2176.
4. Cieply B., Zeng G., Proverbs-Singh T., Geller D.A., Monga S.P. Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene. Hepatology 2009, 49:821-831.
5. van Malenstein H., van Pelt J., Verslype C. Molecular classification of hepatocellular carcinoma anno 2011. Eur. J. Cancer 2011, 47:1789-1797.
6. Guichard C., Amaddeo G., Imbeaud S., Ladeiro Y., Pelletier L., Maad I.B., Calderaro J., Bioulac-Sage P., Letexier M., Degos F., Clément B., Balabaud C., Chevet E., Laurent A., Couchy G., Letouzé E., Calvo F., Zucman-Rossi J. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat. Genet. 2012, 44:694-698.
7. Jesssica Z.R. Molecular classification of HCC. Digestive Liver Disease 2010, 42(Suppl 3):S235-S241.
8. Fujimoto A., Totoki Y., Abe T., Boroevich K.A., Hosoda F., Nguyen H.H., Aoki M., Hosono N., Kubo M., Miya F., Arai Y., Takahashi H., Shirakihara T., Nagasaki M., Shibuya T., Nakano K., Watanabe-Makino K., Tanaka H., Nakamura H., Kusuda J., Ojima H., Shimada K., Okusaka T., Ueno M., Shigekawa Y., Kawakami Y., Arihiro K., Ohdan H., Gotoh K., Ishikawa O., Ariizumi S., Yamamoto M., Yamada T., Chayama K., Kosuge T., Yamaue H., Kamatani N., Miyano S., Nakagama H., Nakamura Y., Tsunoda T., Shibata T., Nakagawa H. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat. Genet. 2012, 44:760-764.
9. Nakagawa H., Shibata T. Comprehensive genome sequencing of the liver cancer genome. Cancer Lett. 2013, 340:234-240.
10. Li M., Zhao H., Zhang X., Wood L.D., Anders R.A., Choti M.A., Pawlik T.M., Daniel H.D., Kannangai R., Offerhaus G.J., Velculescu V.E., Wang L., Zhou S., Vogelstein B., Hruban R.H., Papadopoulos N., Cai J., Torbenson M.S., Kinzler K.W. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat. Genet. 2011, 43:828-829.
11. Huang J., Deng Q., Wang Q., Li K.Y., Dai J.H., Li N., Zhu Z.D., Zhou B., Liu X.Y., Liu R.F., Fei Q.L., Chen H., Cai B., Zhou B., Xiao H.S., Qin L.X., Han Z.G. Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat. Genet. 2012, 44:1117-1121.
12. Chan K., Wong C., Kwan J.S., Lee J.M., Cheung K.W., Yuen M.F., Lai C.L., Poon R.T., Sham P.C., Ng I.O. Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection. PLoS ONE 2011, 6:e28798.
13. Jia D., Wei L., Guo W., Zha R., Bao M., Chen Z., Zhao Y., Ge C., Zhao F., Chen T., Yao M., Li J., Wang H., Gu J., He X. Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma. Hepatology 2011, 54:1227-1236.
14. Toh S., Jin Y., Liu L., Wang J., Babrzadeh F., Gharizadeh B., Ronaghi M., Toh H.C., Chow P.K., Chung A.Y., Ooi L.L., Lee C.G. Deep sequencing of the Hepatitis B Virus in Hepatocellular Carcinoma patients reveals enriched integration events, structural alterations and sequence variations. Carcinogenesis 2012, 4:787-798.
15. Sung W.K., Zheng H., Li S., Chen R., Liu X., Li Y., Lee N.P., Lee W.H., Ariyaratne P.N., Tennakoon C., Mulawadi F.H., Wong K.F., Liu A.M., Poon R.T., Fan S.T., Chan K.L., Gong Z., Hu Y., Lin Z., Wang G., Zhang Q., Barber T.D., Chou W.C., Aggarwal A., Hao K., Zhou W., Zhang C., Hardwick J., Buser C., Xu J., Kan Z., Dai H., Mao M., Reinhard C., Wang J., Luk J.M. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat. Genet. 2012, 44:765-769.
16. Jiang Z., Jhunjhunwala S., Liu J., Haverty P.M., Kennemer M.I., Guan Y., Lee W., Carnevali P., Stinson J., Johnson S., Diao J., Yeung S., Jubb A., Ye W., Wu T.D., Kapadia S.B., de Sauvage F.J., Gentleman R.C., Stern H.M., Seshagiri S., Pant K.P., Modrusan Z., Ballinger D.G., Zhang Z. The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Res. 2012, 22:593-601.
17. Zhang H., Zhai Y., Hu Z., Wu C., Qian J., Jia W., Ma F., Huang W., Yu L., Yue W., Wang Z., Li P., Zhang Y., Liang R., Wei Z., Cui Y., Xie W., Cai M., Yu X., Yuan Y., Xia X., Zhang X., Yang H., Qiu W., Yang J., Gong F., Chen M., Shen H., Lin D., Zeng Y.X., He F., Zhou G. Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat. Genet. 2010, 42:755-758.
18. Jiang D., Sun J., Cao G., Liu Y., Lin D., Gao Y.Z., Ren W.H., Long X.D., Zhang H., Ma X.P., Wang Z., Jiang W., Chen T.Y., Gao Y., Sun L.D., Long J.R., Huang H.X., Wang D., Yu H., Zhang P., Tang L.S., Peng B., Cai H., Liu T.T., Zhou P., Liu F., Lin X., Tao S., Wan B., Sai-Yin H.X., Qin L.X., Yin J., Liu L., Wu C., Pei Y., Zhou Y.F., Zhai Y., Lu P.X., Tan A., Zuo X.B., Fan J., Chang J., Gu X., Wang N.J., Li Y., Liu Y.K., Zhai K., Zhang H., Hu Z., Liu J., Yi Q., Xiang Y., Shi R., Ding Q., Zheng W., Shu X.O., Mo Z., Shugart Y.Y., Zhang X.J., Zhou G., Shen H., Zheng S.L., Xu J., Yu L. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat. Genet. 2013, 45:72-75.
19. Sung W., Zheng H., Li S., Chen R., Liu X., Li Y., Lee N.P., Lee W.H., Ariyaratne P.N., Tennakoon C., Mulawadi F.H., Wong K.F., Liu A.M., Poon R.T., Fan S.T., Chan K.L., Gong Z., Hu Y., Lin Z., Wang G., Zhang Q., Barber T.D., Chou W.C., Aggarwal A., Hao K., Zhou W., Zhang C., Hardwick J., Buser C., Xu J., Kan Z., Dai H., Mao M., Reinhard C., Wang J., Luk J.M. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat. Genet. 2012, 44:765-769.
20. Wang C., Yang W., Yan H.X., Luo T., Zhang J., Tang L., Wu F.Q., Zhang H.L., Yu L.X., Zheng L.Y., Li Y.Q., Dong W., He Y.Q., Liu Q., Zou S.S., Lin Y., Hu L., Li Z., Wu M.C., Wang H.Y. Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice. Hepatology 2012, 55:108-120.
21. Fung J., Lai C., Yuen M.F. Hepatitis B and C virus-related carcinogenesis. Clin. Microbiol. Infect. 2009, 15:964-970.
22. Block T., Mehta A., Fimmel C., Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene 2003, 22:5093-5107.
23. Pikarsky E., Porat R., Stein I., Abramovitch R., Amit S., Kasem S., Gutkovich-Pyest E., Urieli-Shoval S., Galun E., Ben-Neriah Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004, 431:461-466.
24. Naugler W., Sakurai T., Kim S., Maeda S., Kim K., Elsharkawy A.M., Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007, 317:121-124.
25. Hodge D., Hurt E., Farrar W. The role of IL-6 and STAT3 in inflammation and cancer. Eur. J. Cancer 2005, 41:2502-2512.
26. Lu H., Ouyang W., Huang C. Inflammation, a key event in cancer development. Mol. Cancer Res. 2006, 4:221-233.
27. Nikolaou K., Sarris M., Talianidis I. Molecular pathways: the complex roles of inflammation pathways in the development and treatment of liver cancer. Clin. Cancer Res. 2013, 19:2810-2816.
28. Ding J., Li J., Xue C., Wu K., Ouyang W., Zhang D., Yan Y., Huang C. Cyclooxygenase-2 induction by arsenite is through a nuclear factor of activated T-cell-dependent pathway and plays an antiapoptotic role in Beas-2B cells. J. Biol. Chem. 2006, 281:24405-24413.
29. Tong W. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat. Rev. 2006, 32:28-44.
30. Martin M., Herceg Z. From hepatitis to hepatocellular carcinoma: a proposed model for cross-talk between inflammation and epigenetic mechanisms. Genome Med. 2012, 4:8.
31. Junfang J., Jiong S., Budhu A., Yu Z., Forgues M., Roessler S., Ambs S., Chen Y., Meltzer P.S., Croce C.M., Qin L.X., Man K., Lo C.M., Lee J., Ng I.O., Fan J., Tang Z.Y., Sun H.C., Wang X.W. MicroRNA expression, survival, and response to interferon in liver cancer. N. Engl. J. Med. 2009, 361:1437-1447.
32. Wang H.Y., Ding J. Molecular signaling in hepatocellular carcinoma. Molecular Genetics in Liver Neoplasia 2011, 337-348. Springer Science+Business Media, Berlin. first ed. X.W. Wang, G. Grisham, S.S. Thorgeirsson (Eds.).
33. McClendon A., Dean J.L., Ertel A., Fu Z., Rivadeneira D.B., Reed C.A., Bourgo R.J., Witkiewicz A., Addya S., Mayhew C.N., Grimes H.L., Fortina P., Knudsen E.S. RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage. Gastroenterology 2011, 141:1439-1450.
34. Mayhew C., Carter S.L., Fox S.R., Sexton C.R., Reed C.A., Srinivasan S.V., Liu X., Wikenheiser-Brokamp K., Boivin G.P., Lee J.S., Aronow B.J., Thorgeirsson S.S., Knudsen E.S. RB loss abrogates cell cycle control and genome integrity to promote liver tumorigenesis. Gastroenterology 2007, 133:976-984.
35. Nishimura T., Kohara M., Izumi K., Kasama Y., Hirata Y., Huang Y., Shuda M., Mukaidani C., Takano T., Tokunaga Y., Nuriya H., Satoh M., Saito M., Kai C., Tsukiyama-Kohara K. Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase. J. Biol. Chem. 2009, 284:36442-36452.
36. Azechi H., Nishida N., Fukuda Y., Nishimura T., Minata M., Katsuma H., Kuno M., Ito T., Komeda T., Kita R., Takahashi R., Nakao K. Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology. 2001, 60:346-354.
37. Joo M., Kang Y.K., Kim M.R., Lee H.K., Jang J.J. Cyclin D1 overexpression in hepatocellular carcinoma. Liver 2001, 21:89-95.
38. Hui A.M., Sakamoto M., Kanai Y., Ino Y., Gotoh M., Yokota J., Hirohashi S. Inactivation of p16INK4 in hepatocellular carcinoma. Hepatology 1996, 24:575-579.
39. Hsu H., Jeng Y.M., Mao T.L., Chu J.S., Lai P.L., Peng S.Y. Betacatenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am. J. Pathol. 2000, 157:763-770.
40. Hu T.H., Huang C.C., Lin P.R., Chang H.W., Ger L.P., Lin Y.W., Changchien C.S., Lee C.M., Tai M.H. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 2003, 97:1929-1940.
41. Higashitsuji H., Itoh K., Nagao T., Dawson S., Nonoguchi K., Kido T., Mayer R.J., Arii S., Fujita J. Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Nat. Med. 2000, 6:96-99.
42. Higashitsuji H., Higashitsuji H., Itoh K., Sakurai T., Nagao T., Sumitomo Y., Masuda T., Dawson S., Shimada Y., Mayer R.J., Fujita J. The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Cancer Cell 2005, 8:75-87.
43. Li H., Fu X., Chen Y., Hong Y., Tan Y., Cao H., Wu M., Wang H. Use of adenovirusdelivered siRNA to target oncoprotein p28GANK in hepatocellular carcinoma. Gastroenterology 2005, 128:2029-2041.
44. Wen S., Ding J., Wu K., Ning B.F., Wen W., Sun H.Y., Han T., Huang L., Dong L.W., Yang W., Deng X., Li Z., Wu M.C., Feng G.S., Xie W.F., Wang H.Y. Gankyrin-mediated dedifferentiation facilitates the tumorigenicity of hepatocytes and hepatoma cells. Hepatology 2011, 54:1259-1272.
45. Lihua M., Ji Y., Bakiri L., Qiu Z., Cen J., Chen X., Chen L., Scheuch H., Zheng H., Qin L., Zatloukal K., Hui L., Wagner E.F. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat. Cell Biol. 2012, 14:1203-1211.
46. Strazzabosco M., Fabris L. Notch signaling in hepatocellular carcinoma: guilty in association. Gastroenterology 2012, 143:1430-1434.
47. J Ding, Y Feng, Wang H. From cell signaling to cancer therapy. Acta Pharmacol Sin. 2007, 28:1494-1498.
48. Villanueva A., Alsinet C., Yanger K., Hoshida Y., Zong Y., Toffanin S., Rodriguez-Carunchio L., Solé M., Thung S., Stanger B.Z., Llovet J.M. Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology 2012, 143:1660-1669.
49. Wang Y., Han C., Lu L., Magliato S., Wu T. Hedgehog signaling pathway regulates autophagy in human hepatocellular carcinoma cells. Hepatology 2013, 58:995-1010.
50. Llovet J., Ricci S., Mazzaferro V., Hilgard P., Gane E., Blanc J.F., de Oliveira A.C., Santoro A., Raoul J.L., Forner A., Schwartz M., Porta C., Zeuzem S., Bolondi L., Greten T.F., Galle P.R., Seitz J.F., Borbath I., Häussinger D., Giannaris T., Shan M., Moscovici M., Voliotis D., Bruix J. SHARP investigators study group. Sorafenib in advanced hepatocellular carcinoma. Engl. J. Med. 2008, 359:378-390.
51. Schiffer E., Housset C., Cacheux W., Wendum D., Desbois-Mouthon C., Rey C., Clergue F., Poupon R., Barbu V., Rosmorduc O. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology 2005, 41:307-314.
52. Schepers A., Snippert H.J., Stange D.E., Van Den Born M., Van Es J.H., Van De Wetering M., Clevers H. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 2012, 337:730-735.
53. Stewart S., Hyam L. Liver cancer stem cells. J. Clin. Oncol. 2008, 26:2800-2805.
54. Lee J., Heo J., Libbrecht L., Chu I.S., Kaposi-Novak P., Calvisi D.F., Mikaelyan A., Roberts L.R., Demetris A.J., Sun Z., Nevens F., Roskams T., Thorgeirsson S.S. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat. Med. 2006, 12:410-416.
55. Magee J., Piskounova E., Morrison S. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012, 21:283-296.
56. Ma S., Chan K.W., Hu L., Lee T.K., Wo J.Y., Ng I.O., Zheng B.J., Guan X.Y. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 2007, 132:2542-2556.
57. Yang Z., Ho D.W., Ng M.N., Lau C.K., Yu W.C., Ngai P., Chu P.W., Lam C.T., Poon R.T., Fan S.T. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008, 13:153-166.
58. Yang Z.F., Ngai P., Ho D.W., Yu W.C., Ng M.N., Lau C.K., Li M.L., Tam K.H., Lam C.T., Poon R.T., Fan S.T. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 2008, 47:919-928.
59. Yamashita T., Ji J., Budhu A., Forgues M., Yang W., Wang H.Y., Jia H., Ye Q., Qin L.X., Wauthier E., Reid L.M., Minato H., Honda M., Kaneko S., Tang Z.Y., Wang X.W. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009, 136:1012-1024.
60. Xie Z., Choong P.F., Poon L.F., Zhou J., Khng J., Jasinghe V.J., Palaniyandi S., Chen C.S. Inhibition of CD44 expression in hepatocellular carcinoma cells enhances apoptosis, chemosensitivity, and reduces tumorigenesis and invasion. Cancer Chemother. Pharmacol. 2008, 62:949-957.
61. Haraguchi N., Ishii H., Mimori K., Tanaka F., Ohkuma M., Kim H.M., Akita H., Takiuchi D., Hatano H., Nagano H., Barnard G.F., Doki Y., Mori M. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 2010, 120:3326-3339.
62. Lee T., Castilho A., Cheung V.C., Tang K.H., Ma S., Ng I.O. CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 2011, 9:50-63.
63. Yang W., Yan H.X., Chen L., Liu Q., He Y.Q., Yu L.X., Zhang S.H., Huang D.D., Tang L., Kong X.N., Chen C., Liu S.Q., Wu M.C., Wang H.Y. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res. 2008, 68:4287-4295.
64. Qian Y.W., Chen Y., Yang W., Fu J., Cao J., Ren Y.B., Zhu J.J., Su B., Luo T., Zhao X.F., Dai R.Y., Li J.J., Sun W., Wu M.C., Feng G.S., Wang H.Y. P28(GANK) prevents degradation of Oct4 and promotes expansion of tumor-initiating cells in hepatocarcinogenesis. Gastroenterology 2012, 142:1547-1558.
65. Xu X., Nakamura K., Hijioka S., Kamei A., Ikari T., Ishikawa Y., Shinozaki E., Mizunuma N., Hatake K., Miyajima A. DLK as a potential target against cancer stem/progenitor cells of hepatocellular carcinoma. Mol. Cancer Ther. 2012, 11:629-638.
66. Ma S., Chan K.W., Lee T.K., Tang K.H., Wo J.Y., Zheng B.J., Guan X.Y. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol. Cancer Res. 2008, 6:1146-1153.
67. Liu S., Li N., Yu X., Xiao X., Cheng K., Hu J., Wang J., Zhang D., Cheng S., Liu S. Expression of intercellular adhesion molecule 1 by hepatocellular carcinoma stem cells and circulating tumor cells. Gastroenterology 2013, 144:1031-1041.
68. Dreesen O., Brivanlou A. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. 2007, 3:7-17.
69. Lee T.K., Cheung V.C., Ng I.O. Liver tumor-initiating cells as a therapeutic target for hepatocellular carcinoma. Cancer Lett. 2013, 338:101-109.
70. Ning B.F., Ding J., Yin C., Zhong W., Wu K., Zeng X., Yang W., Chen Y.X., Zhang J.P., Zhang X., Wang H.Y., Xie W.F. Hepatocyte nuclear factors 4α prevents the development of hepatocellular carcinoma. Cancer Res. 2010, 70:7640-7651.
71. You H., Ding W., Dang H., Jiang Y., Rountree C.B. C-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma. Hepatology 2011, 54:879-889.
72. Knight B., Tirnitz-Parker J., Olynyk J. C-kit inhibition by imatinib mesylate attenuates progenitor cell expansion and inhibits liver tumor formation in mice. Gastroenterology 2008, 135:969-979.
73. Lee K., Castilho A., Cheung V.C., Tang K.H., Ma S., Ng I.O. Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Hepatology 2011, 53:160-170.
74. Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology 2004, 39:1477-1487.
75. Yang X., Xu Y., Yu B., Zhou J., Qiu S.J., Shi G.M., Zhang B.H., Wu W.Z., Shi Y.H., Wu B., Yang G.H., Ji Y., Fan J. High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut 2010, 59:953-962.
76. Mishra L., Banker T., Murray J., Byers S., Thenappan A., He A.R., Shetty K., Johnson L., Reddy E.P. Liver stem cells and hepatocellular carcinoma. Hepatology 2009, 49:318-329.
77. He G., Dhar D., Nakagawa H., Font-Burgada J., Ogata H., Jiang Y., Shalapour S., Seki E., Yost S.E., Jepsen K., Frazer K.A., Harismendy O., Hatziapostolou M., Iliopoulos D., Suetsugu A., Hoffman R.M., Tateishi R., Koike K., Karin M. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 2013, 155:384-396.
78. Tang Y., Kitisin K., Jogunoori W., Li C., Deng C.X., Mueller S.C., Ressom H.W., Rashid A., He A.R., Mendelson J.S., Jessup J.M., Shetty K., Zasloff M., Mishra B., Reddy E.P., Johnson L., Mishra L. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc. Natl. Acad. Sci. USA 2008, 105:2445-2450.
79. Wu K., Ding J., Chen C., Sun W., Ning B.F., Wen W., Huang L., Han T., Yang W., Wang C., Li Z., Wu M.C., Feng G.S., Xie W.F., Wang H.Y. Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development. Hepatology 2012, 56:2255-2267.
80. Zhao W., Wang L., Han H., Jin K., Lin N., Guo T., Chen Y., Cheng H., Lu F., Fang W., Wang Y., Xing B., Zhang Z. 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel α21 subunit. Cancer Cell 2013, 23:541-556.
81. Wen W., Han T., Chen C., Huang L., Sun W., Wang X., Chen S.Z., Xiang D.M., Tang L., Cao D., Feng G.S., Wu M.C., Ding J., Wang H.Y. Cyclin G1 expands liver tumor-initiating cells by Sox2 induction via Akt/mTOR signaling. Mol. Cancer Ther. 2013, 12:1796-1804.
82. Lee T., Castilho A., Ma S., Ng I.O. Liver cancer stem cells: implications for a new therapeutic target. Liver Int. 2009, 29:955-965.
83. Rebecca S., Deepa N., Ahmedin J. Cancer Statistics 2012, 62:10-29.
84. Ma W., Hsu C.L., Wu M.H., Wu C.T., Wu C.C., Lai J.J., Jou Y.S., Chen C.W., Yeh S., Chang C. Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. Gastroenterology 2008, 135:947-955.
85. Lin H., Yu I.C., Wang R.S., Chen Y.T., Liu N.C., Altuwaijri S., Hsu C.L., Ma W.L., Jokinen J., Sparks J.D., Yeh S., Chang C. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 2008, 47:1924-1935.
86. Wu M., Ma W.L., Hsu C.L., Chen Y.L., Ou J.H., Ryan C.K., Hung Y.C., Yeh S., Chang C. Androgen receptor promotes hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus RNA transcription. Sci. Transl. Med. 2010, 32:32-35.
87. Feng H., Cheng A.S., Tsang D.P., Li M.S., Go M.Y., Cheung Y.S., Zhao G.J., Ng S.S., Lin M.C., Yu J., Lai P.B., To K.F., Sung J.J. Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives β-catenin/T cell factor-dependent hepatocarcinogenesis. J Clin Invest. 2011, 121:3159-3175.
88. Ander S., Trautwein C., Liedtke C. Is interleukin-6 a gender-specific risk factor for liver cancer?. Hepatology 2007, 46:1304-1305.
89. Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc. Natl. Acad. Sci. 2004, 101:15724-15729.
90. Zhao Y., Wang X., Wang T., Hu X., Hui X., Yan M., Gao Q., Chen T., Li J., Yao M., Wan D., Gu J., Fan J., He X. Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization. Hepatology 2011, 53:493-503.
91. Koh W., Wang R., Jin A., Yu M.C., Yuan J.M. Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese health study. Br. J. Cancer 2013, 108:1182-1188.
92. Calle E., Rodriguez C., Walker-Thurmond K., Thun M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003, 348:1625-1638.
93. Baffy G. Editorial: hepatocellular carcinoma in type 2 diabetes: more than meets the eye. Am. J. Gastroenterol. 2012, 107:53-55.
94. Polesel J., Zucchetto A., Montella M., Dal Maso L., Crispo A., La Vecchia C., Serraino D., Franceschi S., Talamini R. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann. Oncol. 2009, 20:353-357.
95. Toffanin S., Friedman S., Llovet J. Obesity, inflammatory signaling, and hepatocellular carcinoma-an enlarging link. Cancer Cell 2010, 17:115-117.
96. Arase Y., Kobayashi M., Suzuki F., Suzuki Y., Kawamura Y., Akuta N., Kobayashi M., Sezaki H., Saito S., Hosaka T., Ikeda K., Kumada H., Kobayashi T. Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C. Hepatology 2013, 57:964-973.
97. Li Q., Li W.W., Yang X., Fan W.B., Yu J.H., Xie S.S., Liu L., Ma L.X., Chen S.J., Kato N. Type 2 diabetes and hepatocellular carcinoma: a case-control study in patients with chronic hepatitis B. Int. J. Cancer 2012, 131:1197-1202.
98. Park E., Lee J.H., Yu G.Y., He G., Ali S.R., Holzer R.G., Osterreicher C.H., Takahashi H., Karin M. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010, 140:197-208.
99. Schlesinger S., Aleksandrova K., Pischon T., Fedirko V., Jenab M., Trepo E., Boffetta P., Dahm C.C., Overvad K., Tjønneland A., Halkjær J., Fagherazzi G., Boutron-Ruault M.C., Carbonnel F., Kaaks R., Lukanova A., Boeing H., Trichopoulou A., Bamia C., Lagiou P., Palli D., Grioni S., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., van den Berg S., Peeters P.H., Braaten T., Weiderpass E., Quirós J.R., Travier N., Sánchez M.J., Navarro C., Barricarte A., Dorronsoro M., Lindkvist B., Regner S., Werner M., Sund M., Khaw K.T., Wareham N., Travis R.C., Norat T., Wark P.A., Riboli E., Nöthlings U. Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. Int. J. Cancer 2013, 132:645-657.
100. Sun B., Karin M. Obesity, inflammation, and liver cancer. J. Hepatol. 2012, 56:704-713.
101. Polina I., Lubov T., Nikolai A. Intracellular signaling and hepatocellular carcinoma. Semin. Cancer Biol. 2011, 21:28-34.
102. Maeda S., Kamata H., Luo L., Leffert H., Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005, 121:977-990.
103. Zhang X., Tan X., Zeng G., Misse A., Singh S., Kim Y., Klaunig J.E., Monga S.P. Conditional beta-catenin loss in mice promotes chemical hepatocarcinogenesis: role of oxidative stress and platelet-derived growth factor receptor alpha/phosphoinositide 3-kinase signaling. Hepatology 2010, 52:954-965.
104. Bard-Chapeau E., Li S., Ding J., Zhang S.S., Zhu H.H., Princen F., Fang D.D., Han T., Bailly-Maitre B., Poli V., Varki N.M., Wang H., Feng G.S. Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 2011, 19:629-639.
105. Zanetti A., Van P., Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine 2008, 26:6266-6273.
106. Sainz B., Heeschen C. Standing out from the crowd: cancer stem cells in hepatocellular carcinoma. Cancer Cell 2013, 23:431-433.